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1.
杜玲玲  徐佳骏  崔岚 《中国药师》2013,16(8):1245-1247
全世界目前约有五千万癫痫患者[1],尽管目前临床上应用的抗癫痫药已有数十种,但仍有1/3左右的患者因为耐药而出现癫痫无法控制[2],亟需新作用机制抗癫痫药物予以治疗.吡仑帕奈(perampanel)是由卫材制药(EISAI INC)开发的世界首例非竞争性α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体拮抗药(图1),2012年7月和10月分别被欧洲EMA和美国FDA批准,用于对12岁以上、伴有或不伴有继发性全身大发作的部分发作癫痫病患者进行辅助治疗.本文对吡仑帕奈的作用机制、药动学、临床研究、药物相互作用等作一综述.  相似文献   

2.
目的研究吡仑帕奈原料药的有关物质来源与合成方法,为产品质量控制提供依据和有关物质对照品。方法根据文献公开报道的吡仑帕奈大规模制备工艺路线和吡仑帕奈分子结构特点,分析吡仑帕奈原料药生产和储存过程中可能存在的有关物质;以2-甲氧基-5-溴吡啶为原料合成有关物质A~G、以2-氰基氯苯为原料合成有关物质H;利用高效液相色谱法建立吡仑帕奈有关物质的分析方法。结果分析了吡仑帕奈原料药可能存在的10个有关物质(A~J),合成了9个有关物质(A~I),并利用1H-NMR和MS进行了结构确证,各有关物质的纯度在99.0%或以上,初步建立了吡仑帕奈原料药有关物质的高效液相色谱分析方法。结论本研究可为吡仑帕奈原料药有关物质的合成提供技术方法,所建立的有关物质分析方法可以为生产吡仑帕奈原料药的质量控制提供参考。  相似文献   

3.
癫痫持续状态(status epilepticus,SE)是严重的神经科急症,会造成大脑神经元损伤,具有潜在致死性。吡仑帕奈是新型口服抗癫痫药,临床上用于多种类型癫痫的治疗。但由于在我国上市时间短,临床应用经验不足,尤其用于儿童SE治疗尚无报道。本文选取4例诊断为SE并使用吡仑帕奈辅助治疗的儿童病例,通过对临床表现、用药调整、疾病转归进行总结分析,并结合国内外相关文献,评价吡仑帕奈在儿童中使用的适应证、用法用量、疗效及安全性,以期为临床合理使用吡仑帕奈提供参考。  相似文献   

4.
目的 建立同时测定人血浆中2种第三代抗癫痫药拉考沙胺和吡仑帕奈血浆药物浓度的方法并应用于临床。方法 10例癫痫患者的血浆样品经乙腈沉淀蛋白并以乙腈-水(20∶80,V/V)稀释后,以氯氮平为内标,采用液相色谱-串联质谱法测定拉考沙胺、吡仑帕奈的质量浓度,再通过稀释倍数换算得血浆药物谷浓度。以Welch Ultimate XB-C18为色谱柱,以10 mmol/L甲酸铵溶液为流动相A、甲醇-乙腈-异丙醇(0.2%甲酸)混合溶液(7∶1.5∶1.5,V/V/V)为流动相B进行梯度洗脱,流速为0.4 mL/min,柱温为40℃,进样量为5μL;采用电喷雾离子源以多反应监测模式进行正离子扫描,用于定量分析的离子对分别为m/z 251.2→144.1(拉考沙胺)、m/z 350.2→219.2(吡仑帕奈)、m/z 327.2→270.0(内标)。结果 拉考沙胺、吡仑帕奈检测质量浓度的线性范围分别为0.001 25~0.125μg/mL(r>0.99)、0.037 5~3.75 ng/mL(r>0.99),定量下限分别为0.001 25μg/mL、0.037 5 ...  相似文献   

5.
目的 考察在空腹、餐后条件下健康受试者口服吡仑帕奈片受试制剂和参比制剂体内吡仑帕奈的血药浓度和药动学参数,评价吡仑帕奈片的生物等效性和安全性。方法 采用健康受试者在空腹、餐后的单中心、单剂量、两制剂、随机、开放、两周期、自身交叉对照试验设计的人体生物等效性研究。空腹和餐后组健康受试者分别口服4 mg吡仑帕奈片受试制剂或参比制剂,采用HPLC-MS/MS法测定血浆中吡仑帕奈的浓度,药动学使用Phoenix WinNonlin 8.1软件的非房室模型计算各受试者的药动学参数,使用SAS 9.4软件进行临床安全性统计分析。结果 空腹、餐后试验吡仑帕奈片受试试剂和参比试剂的最大血药浓度(Cmax)分别为(181.20±46.14)、(168.60±47.98),(130.44±28.59)、(139.15±39.99)ng/mL,药时曲线面积(AUC0-t)分别为(7 587.46±2 975.40)、(7 485.88±2 910.03),(7 820.54±3 229.68)、(7 528.88±2 325.94)h·ng/mL。两组吡仑帕奈片两种制剂的主要药动学参数几何均值均在生物等效性80.00%~125.00%。空腹试验组和餐后试验组不良事件发生率分别为46.70%、50.00%,未出现严重不良事件。结论 吡仑帕奈片受试制剂和参比制剂具有生物等效性,单次服用安全且耐受性良好。  相似文献   

6.
目的 建立HPLC测定人血浆中吡仑帕奈浓度的方法并考察其临床应用。方法 采用Agilent ZORBAX SB-C18(4.6 mm×150 mm,5 μm)色谱柱,流动相为0.05%磷酸(pH 3.5)-乙腈(56∶44),流速为1 mL·min–1,柱温为30℃,检测波长为290 nm。测定癫痫患儿的吡仑帕奈浓度并考察影响血药浓度的风险因素。结果 吡仑帕奈在75~2 500 μg·L–1内线性良好,定量限为75 μg·L–1,准确度不超过标示值的±10%,精密度的变异系数均≤5%,回收率为97.6%~101.0%,在实验涉及的各种条件下稳定性良好。利用该方法测定了51例癫痫患儿的吡仑帕奈血浆谷浓度,所得浓度结果为91.6~1 681.9 μg·L–1;年龄影响吡仑帕奈浓度,<5岁患者的吡仑帕奈谷浓度显著低于5~12岁患者,但与≥12岁患者无显著差异。结论 该方法操作简便,具有较高的准确性和灵敏度,能满足吡仑帕奈治疗药物监测的分析要求,年龄对吡仑帕奈的谷浓度存在显著影响。  相似文献   

7.
2012年10月23日,美国食品药品管理局(FDA)批准吡仑帕奈(perampanel)用于12岁及以上癫痫部分性发作患者的辅助治疗,无论患者是否伴有继发性全身发作。吡仑帕奈为α-氨基-3羟基-5甲基4异恶唑受体(AMPAR)拮抗药,通过抑制突触后AMPA受体谷氨酸活性,减少神经元过度兴奋而发挥抗癫痫作用。这是FDA批准的首个具有该作用机理的抗癫痫药物。本文就其药理学、药动学、不良反应、药物相互作用及临床试验结果综述如下。1药理学谷氨酸是中枢神经系统主要的兴奋性递质,涉及一系列过度兴奋的神经系统疾病。谷氨酸受体分为两类:一类为离子型受体,包括:N-甲基-D-天冬氨酸受体(NMDAR)、海人藻酸受体(KAR)和α-氨基-3羟基-5甲基-4异恶唑受体(AMPAR),它们与离子通道偶联,形成受体通道复合物,介导快信号传递;另一类属于代谢型受体(mGluRs),它与膜内G-蛋白偶联,这些受体被激活后通过G-蛋白效应酶、脑内第二信使  相似文献   

8.
目的 系统评价吡仑帕奈治疗难治性癫痫部分发作的有效性与安全性。方法 计算机检索PubMed、EBSCO、EMbase、Cochrane Library、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)和万方数据库,收集吡仑帕奈治疗难治性癫痫部分发作的随机对照试验,检索时限从建库至2017年2月,采用RevMan 5.0软件对各效应指标进行Meta分析。结果 共纳入5项研究,计1 500例患者。Meta分析结果显示:吡仑帕奈组癫痫完全不发作率[OR=3.75,95%CI (1.77,7.93),P=0.000 6]、发作频率减少≥ 50%的患者百分率[OR=2.08,95%CI (1.69,2.56),P<0.001]均高于安慰剂组,差异有统计学意义;吡仑帕奈主要不良反应有眩晕、困倦、头痛、共济失调、鼻咽炎等;吡仑帕奈8 mg和12 mg组总不良反应发生率高于安慰剂组,差异有统计学意义(P<0.05)。结论 吡仑帕奈治疗难治性癫痫部分发作能有效减少癫痫发作频率,且不良反应较轻,患者基本耐受。  相似文献   

9.
目的 探讨左乙拉西坦片联合吡仑帕奈片治疗儿童良性癫痫的临床疗效。方法 选取2020年5月-2021年12月聊城市第二人民医院收治的78例良性癫痫患儿,按随机数字表法将所有患者分为对照组和治疗组,每组各39例。对照组口服吡仑帕奈片,起始剂量根据患儿体质量>30 kg为2 mg/d、20~30 kg为1 mg/d,睡前吞服,每隔2周加量1次,每次加量为1个起始剂量,直至以4 mg/d的剂量维持治疗。治疗组在对照组基础上口服左乙拉西坦片,起始剂量每次10 mg/kg,2次/d,每隔2周加量1次,每次加量为1个起始剂量(如第1次加量后剂量调整为每次20 mg/kg,2次/d),直至以每次30 mg/kg,2次/d的剂量维持治疗。两组疗程均为6个月。观察两组的临床疗效,比较治疗前后两组癫痫发作情况、痫性放电率、事件相关电位P300潜伏期和波幅以及血清高迁移率族蛋白B1(HMGB1)、肿瘤坏死因子(TNF)-α、胶质纤维酸性蛋白(GFAP)、γ-氨基丁酸(GABA)水平。结果 治疗后,治疗组总有效率是94.87%,显著高于对照组的79.49%(P<0.05)。治疗后,两组癫痫发作频率、NHS3评分均显著降低,持续时间均显著缩短(P<0.05);且以治疗组降低更显著(P<0.05)。治疗后,两组痫性放电率、P300潜伏期均显著缩短,P300波幅均显著增加(P<0.05);且以治疗组改善更显著(P<0.05)。治疗后,两组血清HMGB1、TNF-α、GFAP水平均显著下降,血清GABA水平均显著上升(P<0.05);且治疗后,治疗组血清HMGB1、TNF-α、GFAP、GABA水平均显著优于对照组(P<0.05)。结论 左乙拉西坦片联合吡仑帕奈片治疗儿童良性癫痫有确切疗效,在控制患儿癫痫发作、减少痫性放电、改善认知功能方面均可获得较为满意的效果,并可进一步降低血清HMGB1、TNF-α、GFAP水平及升高血清GABA水平,且安全性较好,值得临床推广应用。  相似文献   

10.
目的验证唑吡坦对失眠症的临床疗效和不良反应。方法将142例失眠患者随机分为唑吡坦组(75例)和艾司唑仑组(67例)进行对照研究。两药均为每晚睡前口服,疗程为10天。对患者治疗前、治疗第5及第10天的睡眠状况及不良反应进行评定, 比较两种药物对睡眠障碍患者的疗效及不良反应。结果唑吡坦和艾司唑仑均可明显缩短入睡时间,延长睡眠时间,减少睡眠中断次数,提高睡眠质量,两组疗效的差异无显著性(P>0.05)。唑吡坦组的日间困倦、头昏乏力等不良反应发生率明显低于艾司唑仑组(P<0.01)。结论唑吡坦在治疗失眠症的疗效上与艾司唑仑相当,但残留的镇静作用及不良反应较轻微,与艾司唑仑相比更易于接受。  相似文献   

11.
目的:探讨小儿热性惊厥患儿脑电图的相关影响因素、疾病的相关临床特征,为临床合理有效的诊断治疗提供较为可靠的参考依据。方法:对本院100例小儿热性惊厥6个月~7岁患儿病情发作后的脑电图等临床相关资料予以回顾性的分析总结,同时就疾病的相关临床特征予以探讨。结果:小儿热性惊厥发作时持续时间、发作的具体年龄及发作次数均和脑电图异常情况的发生率有着密切的相关性。结论:小儿热性惊厥发作持续时间、发作年龄及发作次数等是小儿热性惊厥发作后脑电图异常表现的主要相关性因素,在对小儿热性惊厥患儿予以临床治疗时要仔细分析相关因素,及时有效地予以对症治疗,最大程度地提高患儿的生活质量。  相似文献   

12.
Zonisamide is an antiepileptic drug used as adjunctive therapy for refractory partial seizures in adults. Because of the multiple mechanisms of action, it shows a broad spectrum of anticonvulsant activity and has been effective in several types of seizures, including partial and generalized seizures, tonic-clonic seizures and absence seizures in patients unresponsive to other anticonvulsants. Myoclonic epilepsy, Lennox-Gastaut syndrome and infantile spasms have also been treated effectively with zonisamide. Recent clinical studies have demonstrated additional potential for therapeutic use in neuropathic pain, bipolar disorder, migraine, obesity, eating disorders and Parkinson's disease. Despite adverse events, zonisamide is relatively safe and well tolerated in patients, and shows low discontinuation rate. It has a good pharmacokinetic profile and a low drug interaction potential. Zonisamide is considered as a drug that effectively reduces the frequency of partial seizures.  相似文献   

13.
Target pharmacology of topiramate, a new antiepileptic drug   总被引:7,自引:0,他引:7  
Topiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. Since topiramate hardly affects the threshold of the seizure, topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (gamma-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.  相似文献   

14.
帕金森病和癫痫均为常见的神经系统慢性疾病,但帕金森病合并癫痫在临床上较为少见,部分研究显示帕金森病患者癫痫发作风险增加。脑深部电极刺激术为帕金森病外科治疗的主要选择,但其并发症包括癫痫发作,与较高的发病率和死亡率有关。此外,帕金森合并癫痫患者认知障碍风险增加,一线治疗药物胆碱酯酶抑制剂存在着诱发或加重癫痫发作的可能,而唑尼沙胺是目前唯一可用于帕金森病治疗的抗癫痫药物。本文就帕金森病合并癫痫患者治疗过程中的关键问题进行阐述,以期为临床治疗提供参考。  相似文献   

15.
The promise of new antiepileptic drugs   总被引:3,自引:0,他引:3       下载免费PDF全文
Epilepsy is the most common serious disorder of the brain and comprises a wide range of different conditions with varying aetiologies. The long-established antiepileptic drugs (AEDs) control seizures in 50% of patients developing partial seizures, and 60-70% of those developing generalized seizures. Several AEDs were made available in the 1990s. These drugs have efficacy, but have had only a modest impact on those with refractory epilepsies. A 50% seizure reduction, which is commonly used as an endpoint in clinical trials, confers little benefit to a patient. Of the newer AEDs, lamotrigine and oxcarbazepine are now licensed for use as monotherapy and vigabatrin has a monotherapy licence for infantile spasms. Careful and prolonged postmarketing surveillance is essential to detect adverse effects, which may not be evident in premarketing clinical trials. At this time, there are 10 AEDs currently in varying stages of clinical development. Current strategies for selecting an AED for a particular patient are crude. Magnetic resonance spectroscopic measures of cerebral neuro-transmitters and genetic analysis may allow better prediction of which drug is most likely to be efficacious and to have low risk of adverse effects. Present AEDs suppress the occurrence of seizures. Agents that prevent the development of epilepsy and which protect the brain from the consequences of seizures would be of great value, but it will be difficult to prove their effectiveness. At present AEDs are given continually and systemically. Local drug delivery is feasible and could avoid the adverse effects of AEDs. The combination of local drug delivery with prediction of seizure occurrence could revolutionize the treatment of currently refractory epilepsies.  相似文献   

16.
INTRODUCTION: Epilepsy is stratified into idiopathic partial, symptomatic partial, idiopathic generalized (IGE) and symptomatic generalized epilepsies. AREAS COVERED: The epidemiology and clinical characteristics of IGE are reviewed in this paper. Clinically, IGE is characterized by the occurrence of any of the following three seizure types: absence seizures, myoclonic seizures and primarily generalized tonic-clonic seizures. To assess the presence of evidence-based data on the treatment of IGE, the literature was extensively reviewed for studies evaluating the treatment of IGE with various antiepileptic drugs. These studies were stratified into four classes based on recently described criteria. Class I studies were considered as providing evidence of the efficacy of the drug in patients with IGE. Finally, suggestions to evaluate the efficacy of a study drug in patients with IGE are presented. EXPERT OPINION: Based on the reviewed data, there is strong evidence-based data to support the use of valproate and ethosuximide for the treatment of childhood absence seizures; for the use of topiramate as monotherapy or adjunctive therapy for patients with primarily generalized tonic-clonic seizures; for the use of adjunctive therapy with lamotrigine for the treatment of primarily generalized tonic-clonic seizures; and for the use of levetiracetam as adjunctive therapy for the treatment of myoclonic or primarily generalized tonic-clonic seizures. To evaluate a new drug as a potential treatment for patients with IGE requires a rational methodology, discussed in this review.  相似文献   

17.
目的 总结对48例难治性特发性癫痫病人进行外科治疗的实践经验。方法 将特发性癫痫按临床表现结合神经电生理检查分为三种类型,即部分性发作、部分性发作继发全身性发作和全身性发作,并据此分类分别进行不同的手术方法。结果 本组病例外科治疗有效率为91.67%,不同手术方法有效率比较无显著性差异。结论 根据临床表现结合神经电生理检查并采用分类手术原则可能是治疗难治性特发性癫痫的有效途径。  相似文献   

18.
目的:探讨拉莫三嗪单药对局限性发作癫痫患儿治疗效果及不良反应。方法首次确诊为部分性发作癫痫患儿41例加用拉莫三嗪治疗12个月,治疗前后分别观察治疗效果及不良反应。结果拉莫三嗪单药治疗41例患儿12个月,总有效率为92.68%,其中完全控制率为80.49%,有效控制率为12.20%,无效控制率为4.88%,不良反应率为9.51%。结论拉莫三嗪是治疗局限性发作癫痫患儿疗效确切、安全性好、可单药使用的药物。  相似文献   

19.
Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.  相似文献   

20.
加巴喷丁胶囊添加治疗癫痫的临床疗效和安全性   总被引:1,自引:0,他引:1  
目的 :评价国产加巴喷丁的临床疗效和安全性。方法 :采用多中心、双盲、安慰剂对照、平行试验方法观察加巴喷丁添加治疗癫痫部分性发作(PS)和泛化性全身强直 阵挛发作 (SGTCS) 2 4wk。分 2组 :加巴喷丁组 (原基础抗癫痫药 +加巴喷丁胶囊 90 0mg·d- 1) 110例 ,对照组 (原基础抗癫痫药 +安慰剂 ) 10 8例。结果 :加巴喷丁组总有效率5 2 .7% (5 8/ 110 ) ,对照组 31.5 % (34/ 10 8) ,2组比较 ,P <0 .0 1;2组基线期发作次数≥ 4次 (2 8d)病人的疗效比较 ,P <0 .0 5 ;不同发作类型的疗效比较SGTCS >复杂部分性发作 (CPS) >简单部分性发作(SPS) (P <0 .0 1) ;2组痫样放电减少≥ 2 5 %的疗效比较 ,P <0 .0 5。2组不良反应发生率比较差异无显著性 (P >0 .0 5 )。结论 :国产加巴喷丁添加治疗对控制癫痫PS和SGTCS是有效而安全的。  相似文献   

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